Functional properties of the lysosomal amino acid transporter PQLC2
Résumé
The transporter PQLC2 exports cationic amino acids (CAA) derived from lysosomal proteolysis to the cytosol. It is also required for drug therapy of cystinosis (Jézégou et al., PNAS 2012; Liu et al., Science 2012). We previously showed that PQLC2 is electrogenic and sensitive to pH. In this new set of experiments, we investigate the transport mechanism of PQLC2 by the use of the two-electrode voltage clamp technique (TEVC) with a construct that misrouts the protein to the plasma membrane of Xenopus oocytes.
We first show that PQLC2 transports one charge per arginine molecule and is not coupled to protons. It is thus most probably a uniporter. In agreement with this mechanism, PQLC2 is very sensitive to membrane potential. Finally and surprisingly, PQLC2 appears to exchange selectively lysosomal arginine for cytosolic cationic amino acids in an electroneutral transport mecanism. This last property supports a selective role of PQLC2 in mobilizing Arg from lysosomes or in regulating lysosomal Arg level.
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Sciences du Vivant [q-bio]Origine | Fichiers produits par l'(les) auteur(s) |
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